IGF uptake with competitive binding in articular cartilage

Experiments on the transport of radiolabeled Insulin-like Growth Factors (IGF-I and -II) into bovine articular cartilage show differential uptake depending on the relative proportion of IGF-I and -II. In this study, we present a mathematical model describing both the transport and competition of IGF-I and -II for binding sites represented by two functional groupings of IGF binding proteins (IGFBPs). The first grouping has approximately similar binding affinity to both IGF-I and -II (i.e. IGFBPs 1-5), whereas the second group has significantly higher binding preference for IGF-II compared to IGF-I (i.e. IGFBP-6). Using nonlinear least squares, it is shown that the experimental equilibrium competitive binding results can be described using a reversible Langmuir sorption isotherm involving two dominant IGFBP functional groups. After coupling the sorption model with a poromechanical continuum model, parametric studies are carried out to investigate the effect of model changes including IGF boundary conditions and the ratios of the two IGFBP functional groups. The results show that ignoring competitive binding leads to a significant overestimation of total IGF-I uptake, but an underestimation the rate of "free" (physiologically active) IGF-I within the cartilage. An increase of first group of IGFBPs (i.e. IGFBPs 1-5) as has been reported for osteoarthritis, is observed to hinder the bioavailability of free IGF-I in cartilage, even though the total IGF-I uptake is enhanced. Furthermore, the combination of dynamic compression and competitive binding is seen to enhance the IGF-I uptake within cartilage, but this enhancement is overestimated if competitive binding is neglected.